Case 9: What language do cells speak
- How does cell communication work ?
Cell communication usually works through cell signalling. A sending cells sends
secreted messages only target cells can receive through receptors. These signalling
cells are called ligands, molecules that bind specifically to other molecules. The
intercellular signal is converted to intracellular.
3 steps
- Reception: Ligand binds
- Transduction:
- Response: Something happens in cell
Different types of ligands:
Ligands that can enter the cell: Small, hydrophobic, mostly hormones
o Eicosanoids
o Steroids
o AA/protein derivatives
Ligands that bind to the outside of the cell: Water-soluble ligands are polar or
charged and can’t cross the plasma membrane, mostly protein ligands.
How is it activated?
When a ligand binds to a cell-surface receptor, the receptor’s intracellular domain
changes and it activates. This sets off a series of events, the flow of information is
divided by upstream, earlier in the chain, and downstream, later on in the chain.
Many pathways involve second messengers, small, non-protein molecules that
pass along a signal initiated by the binding of a ligand (the “first messenger”) to its
receptor
o Ca2+ ions: upstream signalling events release a ligand that binds to and
opens ligand-gated calcium ion channels. These channels open and allow
the higher levels of Ca2+ that are present outside the cell to flow into the
cytoplasm. Some proteins in the cell have binding sites for Ca2+ ions, and
the released ions attach to these proteins and change their shape and
thus, their activity.
o Cyclic AMP: In response to signals,
adenylyl cyclase converts ATP into
cAMP, removing two phosphates
and linking the remaining phosphate
to the sugar in a ring shape. cAMP
can activate protein kinase A (PKA),
enabling it to phosphorylate its
targets and pass along the signal.
cAMP signalling is turned off by
phosphodiesterase, which break the
ring of cAMP and turn it into
adenosine monophosphate (AMP).
o ATP derivative
o Inositol phosphates: Phospholipids
are phosphorylated and snipped in
half, releasing two fragments that
, both act as second messengers, Pip2. Phospholipase C cleaves Pip2 into
two fragments,
DAG: Stays in the plasma membrane and can activate a target
called protein kinase C (PKC), allowing it to phosphorylate its own
targets
Ip3: diffuses into the cytoplasm and can bind to ligand-gated
calcium channels in the endoplasmic reticulum, releasing Ca2+
that continues the signal cascade.
How is it inhibited?
o Competitive inhibition: Interruption via a
chemical substance inhibiting the effect of
another by competing with it for binding or
bonding. Binding of an inhibitor prevents
binding of the target molecule of the
enzyme
o Non-competitive inhibition: Enzymes
binding an effector molecule at a site other
than the enzyme's active site.
- How does non-physical communication work (external signals)? (paracrine,
endocrine, … )
o Paracrine: Cells communicate over
relatively short distances through
cellular secretion, the release of
chemical messengers.
o Autocrine: A cell targets itself,
releasing a ligand that binds its own
receptors. Receptors can also be
inside, so ligands don’t need to be
released.
o Synaptic (paracrine): Nerve cells
transmit signals, which happens in
the synapse.
The sending neuron fires an
electrical impulse traveling down an
axon. It triggers the release of
ligands called neurotransmitters,
which quickly cross the small gap
between the nerve cells. The
molecules of neurotransmitter
diffuse across the synaptic cleft and bind to receptor proteins on the
postsynaptic cell. Activation of postsynaptic receptors leads to the opening or
closing of ion channels in the cell membrane. This may be depolarizing
—make the inside of the cell more positive—or hyperpolarizing—make
the inside of the cell more negative—depending on the ions involved
Endocrine: Long distance signalling, using the circulatory system
(bloodstream) as distribution network. The signals are produced by
specialized cells.
Gap junctions
Gasses NO2 and O2
- How does cell communication work ?
Cell communication usually works through cell signalling. A sending cells sends
secreted messages only target cells can receive through receptors. These signalling
cells are called ligands, molecules that bind specifically to other molecules. The
intercellular signal is converted to intracellular.
3 steps
- Reception: Ligand binds
- Transduction:
- Response: Something happens in cell
Different types of ligands:
Ligands that can enter the cell: Small, hydrophobic, mostly hormones
o Eicosanoids
o Steroids
o AA/protein derivatives
Ligands that bind to the outside of the cell: Water-soluble ligands are polar or
charged and can’t cross the plasma membrane, mostly protein ligands.
How is it activated?
When a ligand binds to a cell-surface receptor, the receptor’s intracellular domain
changes and it activates. This sets off a series of events, the flow of information is
divided by upstream, earlier in the chain, and downstream, later on in the chain.
Many pathways involve second messengers, small, non-protein molecules that
pass along a signal initiated by the binding of a ligand (the “first messenger”) to its
receptor
o Ca2+ ions: upstream signalling events release a ligand that binds to and
opens ligand-gated calcium ion channels. These channels open and allow
the higher levels of Ca2+ that are present outside the cell to flow into the
cytoplasm. Some proteins in the cell have binding sites for Ca2+ ions, and
the released ions attach to these proteins and change their shape and
thus, their activity.
o Cyclic AMP: In response to signals,
adenylyl cyclase converts ATP into
cAMP, removing two phosphates
and linking the remaining phosphate
to the sugar in a ring shape. cAMP
can activate protein kinase A (PKA),
enabling it to phosphorylate its
targets and pass along the signal.
cAMP signalling is turned off by
phosphodiesterase, which break the
ring of cAMP and turn it into
adenosine monophosphate (AMP).
o ATP derivative
o Inositol phosphates: Phospholipids
are phosphorylated and snipped in
half, releasing two fragments that
, both act as second messengers, Pip2. Phospholipase C cleaves Pip2 into
two fragments,
DAG: Stays in the plasma membrane and can activate a target
called protein kinase C (PKC), allowing it to phosphorylate its own
targets
Ip3: diffuses into the cytoplasm and can bind to ligand-gated
calcium channels in the endoplasmic reticulum, releasing Ca2+
that continues the signal cascade.
How is it inhibited?
o Competitive inhibition: Interruption via a
chemical substance inhibiting the effect of
another by competing with it for binding or
bonding. Binding of an inhibitor prevents
binding of the target molecule of the
enzyme
o Non-competitive inhibition: Enzymes
binding an effector molecule at a site other
than the enzyme's active site.
- How does non-physical communication work (external signals)? (paracrine,
endocrine, … )
o Paracrine: Cells communicate over
relatively short distances through
cellular secretion, the release of
chemical messengers.
o Autocrine: A cell targets itself,
releasing a ligand that binds its own
receptors. Receptors can also be
inside, so ligands don’t need to be
released.
o Synaptic (paracrine): Nerve cells
transmit signals, which happens in
the synapse.
The sending neuron fires an
electrical impulse traveling down an
axon. It triggers the release of
ligands called neurotransmitters,
which quickly cross the small gap
between the nerve cells. The
molecules of neurotransmitter
diffuse across the synaptic cleft and bind to receptor proteins on the
postsynaptic cell. Activation of postsynaptic receptors leads to the opening or
closing of ion channels in the cell membrane. This may be depolarizing
—make the inside of the cell more positive—or hyperpolarizing—make
the inside of the cell more negative—depending on the ions involved
Endocrine: Long distance signalling, using the circulatory system
(bloodstream) as distribution network. The signals are produced by
specialized cells.
Gap junctions
Gasses NO2 and O2
